D.H. Ripin, D.A. Evans pKa's of Inorganic and Oxo-Acids Chem 206

D.H. Ripin, D.A. Evans
pKa's of Inorganic and Oxo-Acids
Chem 206
Substrate
pKa
H 2 O
(DMSO)
Substrate
pKa H 2 O(DMSO)
Substrate
pKa
H 2 O
(DMSO)
Substrate
pKa
H 2 O
(DMSO)
INORGANIC ACIDS
CARBOXYLIC ACIDS
ALCOHOLS
PROTONATED SPECIES
H 2 O
H 3 O +
HOOH
15.7
-1.7
11.6
(32)
H 2 S
7.00
H 3 PO 4 2.12, 7.21,
12.32
HBr
-9.00 (0.9)
HCl
-8.0 (1.8)
HF
3.17 (15)
HOCl
7.5
HClO 4
-10
HCN
9.4 (12.9)
HNO 2 3.29
HN 3 4.72 (7.9)
HSCN
4.00
H 2 SO 3 1.9, 7.21
H 2 SO 4 -3.0, 1.99
HNO 3 -1.3
H 2 CrO 4
-0.98, 6.50
CH 3 SO 3 H
CF 3 SO 3 H
-2.6
-14
(1.6)
(0.3)
9.24
NH 4 Cl
B(OH) 3
9.23
X
O
OH
X= CH 3 4.76 (12.3)
CH 2 NO 2
CH 2 F
CH 2 Cl
CH 2 Br
cis-CO 2 H
1.68
2.66
2.86
2.86
1.29
C 6 H 5
2.17
CH 2 I
3.12
CHCl 2
CCl 3 0.65
CF 3 -0.25
H
3.77
HO
3.6, 10.3
4.2 (11.1)
o-O 2 NC 6 H 4
m-ClC 6 H 4 3.83
m-O 2 NC 6 H 4 2.45
p-O 2 NC 6 H 4 3.44
o-ClC 6 H 4 2.94
p-ClC 6 H 4 3.99
o-(CH 3 ) 3 N + C 6 H 4 1.37
p-(CH 3 ) 3 N + C 6 H 4 3.43
p-OMeC 6 H 4 4.47
O
R
OH
R= H
4.25
trans-CO 2 H 3.02, 4.38
1.92, 6.23
HOH
CF 3 CH 2 OH
(CF 3 ) 2 CHOH
MeOOH
CH 3 CO 3 H
PEROXIDES
15.7
MeOH
15.54 (27.9)
i-PrOH
16.5 (29.3)
t-BuOH
17 (29.4)
c-hex 3 COH 24
C 6 H 5 OH
m-O 2 NC 6 H 4 OH
p-O 2 NC 6 H 4 OH
p-OMeC 6 H 4 OH
12.5
8.35
7.14
11.5
8.2
(31.2)
(23.5)
(17.9)
9.95 (18.0)
(10.8)
10.20 (19.1)
2-napthol (17.1)
OXIMES & HYDROXAMIC ACIDS
Ph
Ph
Ph
N
O
O
OH
Ph
N
H
N
Me
OH
OH
11.3 (20.1)
8.88
(NH)
(13.7)
(18.5)
O
N +
Ph OH
+
OH
Ph OH
+
OH
Ph CH 3
H
O +
Ph Me
H
Me
O+ Me
O + H
H
O +
Me H
+
OH
S
Me Me
N + OH
-12.4
-7.8
-6.2
-6.5
-3.8
-2.05
-2.2
-1.8
0.79
SULFINIC & SULFONIC ACIDS
O O
Me S OH
O
Ph S OH
-2.6
2.1
*Values 14 for water and >35 for DMSO were extrapolated using various methods.

D.H. Ripin, D.A. Evans
pKa's of Nitrogen Acids
Chem 206
Substrate pKa H 2 O (DMSO) Substrate pKa H 2 O (DMSO) Substrate pKa H 2 O (DMSO) Substrate pKa H 2 O (DMSO)
+ 9.2 (10.5) HN 3 4.7 (7.9)
N H 4
EtN + NH
H 3
38 (41)
3
10.6
i-Pr 2 N + i-Pr 2 NH (36 THF))
H 2
11.05
TMS 2 NH 26(THF) (30)
Et 3 N + H
10.75 (9.00) PhNH 2
(30.6)
PhN + H 3
4.6 (3.6) Ph 2 NH
(25.0)
Ph 2 N + H 2 0.78
NH
(44)
2-napthal-N + Me
H 3 4.16
Me
PhN + (Me) 2 H 5.20 (2.50) NCNH 2 (16.9)
H 2 NN + H 3
8.12
HON + H 3 5.96
Quinuclidine 11.0 (9.80)
Morpholine O 8.36
N-Me morpholine 7.38
O 2 N
PROTONATED NITROGEN
DABCO
H
+ NH 3
+ NH 3
H 3 N + + NH 3
Proton Sponge
NO 2
+
N + H
N +
N + H N + H 2
NO 2
NH 3
-9.3
2.97, 8.82
(2.97, 8.93)
6.90, 9.95
-9.0, 12.0
(--, 7.50)
TMP
H 2 N
R= H
CH 3
Ph
CF 3
NH 2 (urea)
OEt
(24.1)
AMINES
15.1
(37)
(26.5)
AMIDES & CARBAMATES
R NH 2
Et
O
O
O
N
H
NH
Ph
N
NH
Me
Me
O
O
(23.5)
(25.5)
(23.3)
(17.2)
(26.9)
(24.8)
(21.6)
12 (20.5)
NH
IMIDES
Ac 2 NH (17.9)
8.88 (13.7)
(17.0)
PhCN + OH
H -10
Ph N
(NH)
Bn
N O
N
H
H
*Values 14 for water and >35 for DMSO were extrapolated using various methods.
8.30
SULFONAMIDE
(14.7)
MeSO 2 NH 2
(17.5)
CF 3 SO 2 NH 2 6.3 (9.7)
PhSO 2 NH 2
(16.1)
MeSO 2 NHPh (12.9)
GUANIDINIUM,
HYRDAZONES,- IDES, & -INES
(13.6)
(21.6)
Ph Me
O
(18.9)
Ph NHNH 2
PhSO 2 NHNH 2 (17.2)
PhNHNHPh (26.1)
O
O
NH
O
N + H 2
Me 2 N NMe 2
NNH 2
O
NH
O
HYDROXAMIC ACID
R
R=
DBU
DMAP
R
+
NH
AMIDINES
R= Me (17.3)
Ph (15.0)
PROTONATED HETEROCYCLES
Me 2 N
NSO 2 Ph
R
+
NH
+
N
H
9.2
(12) (estimate)
+
NH
6.95
H (PPTS) 5.21 (3.4)
t-Bu
4.95 (0.90)
Me 6.75 (4.46)
Cl, H 0.72
NH
NH 2
HETEROCYCLES
H
N
(23.0)
N
HN
HN
(20.95)
N
(18.6)
1,2,3 triazole
N
NH
(13.9)

D.H. Ripin, D.A. Evans
pKa's of CH bonds in Hydrocarbons and Carbonyl Compounds
Chem 206
Substrate pKa H 2 O (DMSO) Substrate pKa H 2 O (DMSO) Substrate pKa H 2 O (DMSO) Substrate pKa H 2 O (DMSO)
CH 2 =CH 2
CH 4
CH 2 =CHCH 3
PhH
PhCH 3
Ph 2 CH 2
Ph 3 CH
HCCH
24
PhCCH 23 (28.8)
H 2
HYDROCARBONS
(Me) 3 CH 53
(Me) 2 CH 2 51
XC 6 H 4 CH 3
X= p-CN
p-NO 2
Me
Me
p-COPh
Me
Me
50
48
46
43
43
41
33.5
31.5
20
15
~36
(56)
(44)
(43)
(32.2)
(30.6)
(30.8)
(20.4)
(26.9)
(26.1)
(20.1)
(18.0)
t-BuO
O
LiO
O
O
t-BuO Me O
Ph
EtO
EtO
MeO
MeO
Me 2 N
O
O
O
Me 2 N
O
Et 2 N
Me 2 N
Me 2 N
N
O
O
O
S
O
S
ESTERS
N + Me 3
O
Ph
Me
Me
O
S
AMIDES
Ph
SPh
OMe
N + Me 3
O
CN
Me
24.5
11
13
(30.3)
(23.6)
(20.0)
(14.2)
(15.7)
(20.9)
[30.2 (THF)]
(26.6)
(25.9)
(24.9)
(17.2)
(18.2)
(25.7)
X= H
Ph
SPh
COCH 3
SO 2 Ph
KETONES
9
(26.5)
(19.8)
(18.7)
(13.3)
(15.1)
19-20 (27.1)
*Values 14 for water and >35 for DMSO were extrapolated using various methods.
Me
Et
i-Pr
O
O
Et
O
O
t-Bu O
Ph
Ph
O
X
i-Pr
Me
i-Pr
X
(28.3)
(27.7)
(26.3)
X= H
CH 3
Ph
COCH 3
COPh
CO 2 Et
CN
F
OMe
(24.7)
(24.4)
(17.7)
(12.7)
(13.3)
(22.7)
(10.2)
(21.6)
(22.85)
OPh
SPh
SePh
NPh 2
(21.1)
(16.9)
(18.6)
(20.3)
N + Me 3
NO 2
(14.6)
(7.7)
SO 2 Ph
(11.4)
X
X= H
OMe
NMe 2
Br
CN
O
n
n=
Me
4
5
6
7
8
O
O
O
O
Me
O
Me
(24.7)
(25.7)
(27.5)
(23.8)
(22.0)
(25.1)
(25.8)
(26.4)
(27.7)
(27.4)
(28.1)
(29.0)
(25.5)
(32.4)

D.H. Ripin, D.A. Evans
pKa's of CH bonds at Nitrile, Heteroaromatic, and Sulfur Substituted Carbon
Chem 206
Substrate pKa H 2 O (DMSO) Substrate pKa H 2 O (DMSO) Substrate pKa H 2 O (DMSO) Substrate pKa H 2 O (DMSO)
NC
X= H
CH 3
Ph
COPh
CONR 2
CO 2 Et
CN
OPh
N + Me 3
SPh
SO 2 Ph
N
N
N
N +
O -
O
S
X
NITRILES
11
HETERO-AROMATICS
Ph
Ph
Ph
Ph
Ph
Ph
(31.3)
(32.5)
(21.9)
(10.2)
(17.1)
(13.1)
(11.1)
(28.1)
(20.6)
(20.8)
(12.0)
(28.2)
(30.1)
(26.7)
(25.2)
(30.2)
(30.0)
PhSCH 2 X
X= Ph
CN
COCH 3
COPh
NO 2
SPh
SO 2 Ph
SO 2 CF 3
POPh 2
MeSCH 2 SO 2 Ph
PhSCHPh 2 (26.7)
(PhS) 3 CH
(22.8)
(PrS) 3 CH
(31.3)
Me
S
(30.5)
S S H
(PhS) 2 CHPh
(23.0)
X=
S
S
X
Ph
CO 2 Me
CN
RSCH 2 CN
R=
Me
Et
i-Pr
t-Bu
SULFIDES
(30.8)
(20.8)
(18.7)
(16.9)
(11.8)
(30.8)
(20.3)
(11.0)
(24.9)
(23.4)
(30.7)
(20.8)
(19.1)
(24.3)
(24.0)
(23.6)
(22.9)
PhSCH=CHCH 2 SPh (26.3)
BuSH
10-11 (17.0)
PhSH
≈7 (10.3)
X= H (35.1)
Ph
(29.0)
SPh (29.0)
H
Ph
SOPh
Me 3 S + =O
SULFONIUM
(33)
(27.2)
(18.2)
*Values 14 for water and >35 for DMSO were extrapolated using various methods.
Me
Ph S X
X=
Ph
Ph
O
S
O
O
S
CHPh 2
SULFOXIDES
X
(24.5)
(18.2)
(16.3)
SULFIMIDES & SULFOXIMINES
NTs
S
Ph R
Ph S Me
R= Me
i-Pr
O NTs
O NMe
S
Ph Me
O N + Me 2
Ph S Me
O NTs
Ph
Me
S+ CH 2 Ph
S
CH 2 Cl
(27.6)
(30.7)
(24.5)
(33)
(14.4)
(20.7)
Ph
O
S
O
SULFONES
X
X= H
(29.0)
CH 3
(31.0)
t-Bu
(31.2)
Ph
(23.4)
CH=CH 2
(22.5)
CH=CHPh
(20.2)
CCH
(22.1)
CCPh
(17.8)
COPh
(11.4)
COMe
(12.5)
OPh
(27.9)
N + Me 3
(19.4)
CN
(12.0)
NO 2
(7.1)
SMe
(23.5)
SPh
(20.5)
SO 2 Ph
(12.2)
PPh 2 (20.2)
O
O
Ph S CHPh 2
O O
S
Me
O
Me
O
S
CF 3 Me
O O
S
CF 3 i-Pr
O O
CF 3
Et
O
S
S
O
Et
(PhSO 2 ) 2 CH 2 Me
(22.3)
(31.1)
(18.8)
(21.8)
(26.6)
(32.8)
(14.3)

D. H. Ripin, D. A. Evans
pKa's of CH bonds at Heteroatom Substituted Carbon & References
Chem 206
Substrate pKa H 2 O (DMSO) Substrate pKa H 2 O (DMSO) Substrate pKa
CH 3 OPh
MeOCH 2 SO 2 Ph
PhOCH 2 SO 2 Ph
PhOCH 2 CN
MeO
X=
CN
O
O
COPh
CO 2 Et
Ph
Me 3 N + CH 2 X
SO 2 Ph
CONEt 2
ETHERS
SELENIDES
AMMONIUM
(49)
(30.7)
(27.9)
(28.1)
(21.1)
PhSe
(18.6)
Ph
PhSeCHPh 2
(27.5)
(PhSe) 2 CH 2 (31.3)
PhSeCH 2 Ph
PhSeCH=CHCH 2 SePh
(31.0)
(27.2)
(20.6)
(19.4)
(14.6)
(20.6)
(24.9)
P + H 4
-14
MeP + H 3 2.7
Et 3 P + H
9.1
Ph 3 P + CH 3 (22.4)
Ph 3 P + i-Pr
(21.2)
Ph 3 P + CH 2 COPh
Ph 3 P + CH 2 CN
(EtO) 2 P
X=
O
Ph 2 P
PHOSPONATES &
PHOSPHINE OXIDES
O
Ph
CN
CO 2 Et
Cl
PHOSPHONIUM
SiMe 3
X
X
X= SPh
(24.9)
CN
(16.9)
Ph 2 PCH 2 PPh 2
PHOSPHINES
Ph 2 PCH 2 SO 2 Ph
(6.2)
(7.0)
(27.6)
(16.4)
(18.6)
(26.2)
(28.8)
(29.9)
(20.3)
RNO 2
R=
O 2 N
n=
Ph
CH 3
CH 2 Me
CHMe 2
CH 2 Ph
CH 2 Bn
CH 2 SPh
CH 2 SO 2 Ph
CH 2 COPh
N
3
4
5
6
7
n
Ph
Ph
NITRO
IMINES
H 2 O (DMSO)
≈10
(17.2)
(16.7)
(16.9)
(12.2)
(16.2)
(11.8)
(7.1)
(7.7)
(26.9)
(17.8)
(16.0)
(17.9)
(15.8)
(24.3)
Oxime ethers are ~ 10 pka units less
acidic than their ketone counterparts
Streitwieser, JOC 1991, 56, 1989
DMSO:
REFERENCES
JACS 97, 7007 (1975)
JACS 97, 7160 (1975)
JACS 97, 442 (1975)
JACS 105, 6188 (1983)
JOC 41, 1883 (1976)
JOC 41, 1885 (1976)
JOC 41, 2786 (1976)
JOC 41, 2508 (1976)
JOC 42, 1817 (1977)
JOC 42, 321 (1977)
JOC 42, 326 (1977)
JOC 43, 3113 (1978)
JOC 43, 3095 (1978)
JOC 43, 1764 (1978)
JOC 45, 3325 (1980)
JOC 45, 3305 (1980)
JOC 45, 3884 (1980)
JOC 46, 4327 (1981)
JOC 46, 632 (1981)
JOC 47, 3224 (1982)
JOC 47, 2504 (1982)
Acc. Chem. Res. 21, 456 (1988)
Unpublished results of F. Bordwell
Water:
Advanced Org. Chem., 3rd Ed.
J. March (1985)
Unpublished results of W. P. Jencks
THF:
JACS 110, 5705 (1988)
*Values 14 for water and >35 for DMSO were extrapolated using various methods.